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Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies

Primary Purpose

Acute Myeloid Leukemia (AML), B-cell Non-Hodgkin's Lymphoma (B-NHL), Multiple Myeloma (MM)

Status
Withdrawn
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Autologous CAR-T cells
Fludarabine
Cyclophosphamide
Sponsored by
Shanghai Pudong Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring CD123 CAR-T, CD19 CAR-T, BCMA CAR-T, CD7 CAR-T, Hematopoietic and Lymphoid Malignancies

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Ability to understand and the willingness to sign informed consent.
  2. Patients with relapsed or refractory Acute Myeloid Leukemia (AML), B-cell Non-Hodgkin's Lymphoma (B-NHL), Multiple Myeloma (MM), Adult T-cell Leukemia/Lymphoma (ATL), B-cell Acute Lymphoblastic Leukemia (B-ALL) after at least two cycles of first-line therapy or autologous hematopoietic stem cell transplantation (auto-HSCT).
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0~2.

  4. Adequate organ functions:

    • Sufficient bone marrow function evaluated by investigator to receive lymphodepleting preparative regimen;
    • Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN), or creatinine clearance rate (as estimated by Cockcroft Gault) > 30 mL/min/1.73 m^2;
    • Alanine aminotransferase (ALT) ≤ 5×ULN; and total bilirubin (TBIL) <2.0mg/dL; TBIL of patients with Gilbert's Syndrome or liver involvement must less than 3.0 mg/dL;
    • Left ventricular ejection fraction (LVEF) > 40%.
  5. Subjects who have previously received CD19 targeted therapy must have biopsy-proven lymphoma lesions still express CD19 antigen.

Exclusion Criteria:

  1. Lymphomas involving only the central nervous system (CNS) (subjects with secondary CNS lymphomas are admitted).
  2. History of another malignancy that has not been in remission for at least 2 year (the following conditions may be excluded from the 2-year restriction: non-melanoma skin cancer, completely resected stage I tumor with low probability of recurrence, limited-stage prostate cancer after treatment, biopsy-proven cervical carcinoma in situ, or PAP smear showing squamous epithelium internal lesions).
  3. History of treatment with Alemtuzumab within 6 months prior to leukapheresis, or Fludarabine or Cladribine within 3 months prior to leukapheresis.
  4. Active hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), or syphilis infection.
  5. Uncontrolled fungal, bacterial, viral, or other infection.
  6. Acute or chronic graft-versus-host disease (GVHD).
  7. History of any of the following cardiovascular diseases within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stent, myocardial infarction, unstable angina, or other clinically significant heart disease.
  8. History or clinical evidence of CNS disease.
  9. Female subjects who are pregnant or lactating.
  10. Prior CAR-T therapy or other genetically modified T cell therapy.

Sites / Locations

  • Shanghai Pudong Hospital, Fudan University Affiliated Pudong Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous CAR-T cells

Arm Description

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR-T cells. CAR-T cells targeted CD19/BCMA/CD123/CD7 are autologous genetically modified T cells.

Outcomes

Primary Outcome Measures

TEAEs
Incidence and severity of Treatment Emergent Adverse Event.
TRAEs
Incidence and severity of Treatment Related Adverse Events.
AESIs
Incidence and severity of AEs of Special Interest.

Secondary Outcome Measures

Duration of Overall Response (DOR)
Time from documentation of disease response to disease progression.
Progression-Free Survival (PFS)
PFS was defined as the time from CAR-T infusion to the date of disease progression or death from any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Overall survival (OS)
OS was defined as the time from CAR-T infusion to the date of death. Participants who did not die by the analysis data cutoff date were censored at their last contact date.

Full Information

First Posted
August 22, 2022
Last Updated
February 27, 2023
Sponsor
Shanghai Pudong Hospital
Collaborators
UTC Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05513612
Brief Title
Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies
Official Title
Safety and Efficacy Study of Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Withdrawn
Why Stopped
The study is not initiated and we want it to be withdrawn.
Study Start Date
August 1, 2020 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Pudong Hospital
Collaborators
UTC Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary purpose of this study is to determine the safety and efficacy of novel autologous CAR-T cells in patients with hematopoietic and lymphoid malignancies.
Detailed Description
Chimeric antigen receptor (CAR)-modified T cells targeted CD19 have demonstrated unprecedented successes. Besides CD19, many other molecules such as CD123, BCMA, and CD7 may be potential in developing the corresponding CAR-T cells to treat patients with hematopoietic and lymphoid malignancies. UTC Therapeutics Inc. have developed an efficient platform for constructing CAR-T cells that can remodel of tumor microenvironment and enhance the anti-tumor immune response and persistence of CAR-T cells. In this study, all eligible subjects will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by investigational treatment, CAR-T cells. Safety, efficacy, pharmacokinetic, and pharmacodynamic of the CAR-T cells will be assessed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML), B-cell Non-Hodgkin's Lymphoma (B-NHL), Multiple Myeloma (MM), T-Cell Leukemia/Lymphoma, Adult, B-cell Acute Lymphoblastic Leukemia (B-ALL)
Keywords
CD123 CAR-T, CD19 CAR-T, BCMA CAR-T, CD7 CAR-T, Hematopoietic and Lymphoid Malignancies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Autologous CAR-T cells
Arm Type
Experimental
Arm Description
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR-T cells. CAR-T cells targeted CD19/BCMA/CD123/CD7 are autologous genetically modified T cells.
Intervention Type
Biological
Intervention Name(s)
Autologous CAR-T cells
Intervention Description
CAR-T cells will be infused intravenously.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Administered according to package insert
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Administered according to package insert
Primary Outcome Measure Information:
Title
TEAEs
Description
Incidence and severity of Treatment Emergent Adverse Event.
Time Frame
4 weeks
Title
TRAEs
Description
Incidence and severity of Treatment Related Adverse Events.
Time Frame
4 weeks
Title
AESIs
Description
Incidence and severity of AEs of Special Interest.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Duration of Overall Response (DOR)
Description
Time from documentation of disease response to disease progression.
Time Frame
12 months
Title
Progression-Free Survival (PFS)
Description
PFS was defined as the time from CAR-T infusion to the date of disease progression or death from any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Time Frame
12 months
Title
Overall survival (OS)
Description
OS was defined as the time from CAR-T infusion to the date of death. Participants who did not die by the analysis data cutoff date were censored at their last contact date.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to understand and the willingness to sign informed consent. Patients with relapsed or refractory Acute Myeloid Leukemia (AML), B-cell Non-Hodgkin's Lymphoma (B-NHL), Multiple Myeloma (MM), Adult T-cell Leukemia/Lymphoma (ATL), B-cell Acute Lymphoblastic Leukemia (B-ALL) after at least two cycles of first-line therapy or autologous hematopoietic stem cell transplantation (auto-HSCT). Eastern Cooperative Oncology Group (ECOG) performance status of 0~2. Adequate organ functions: Sufficient bone marrow function evaluated by investigator to receive lymphodepleting preparative regimen; Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN), or creatinine clearance rate (as estimated by Cockcroft Gault) > 30 mL/min/1.73 m^2; Alanine aminotransferase (ALT) ≤ 5×ULN; and total bilirubin (TBIL) <2.0mg/dL; TBIL of patients with Gilbert's Syndrome or liver involvement must less than 3.0 mg/dL; Left ventricular ejection fraction (LVEF) > 40%. Subjects who have previously received CD19 targeted therapy must have biopsy-proven lymphoma lesions still express CD19 antigen. Exclusion Criteria: Lymphomas involving only the central nervous system (CNS) (subjects with secondary CNS lymphomas are admitted). History of another malignancy that has not been in remission for at least 2 year (the following conditions may be excluded from the 2-year restriction: non-melanoma skin cancer, completely resected stage I tumor with low probability of recurrence, limited-stage prostate cancer after treatment, biopsy-proven cervical carcinoma in situ, or PAP smear showing squamous epithelium internal lesions). History of treatment with Alemtuzumab within 6 months prior to leukapheresis, or Fludarabine or Cladribine within 3 months prior to leukapheresis. Active hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), or syphilis infection. Uncontrolled fungal, bacterial, viral, or other infection. Acute or chronic graft-versus-host disease (GVHD). History of any of the following cardiovascular diseases within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stent, myocardial infarction, unstable angina, or other clinically significant heart disease. History or clinical evidence of CNS disease. Female subjects who are pregnant or lactating. Prior CAR-T therapy or other genetically modified T cell therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhiguo Long
Organizational Affiliation
Shanghai Pudong Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Pudong Hospital, Fudan University Affiliated Pudong Medical Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201399
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies

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